Introducing three T-CiRA researchers working on the clinical application of iPS cell technology
T-CiRA is a 10-year-long joint research program between Takeda and Kyoto University's Center for iPS Cell Research and Application (CiRA) led by Prof. Shinya Yamanaka, a Nobel Prize-winning researcher. T-CiRA is engaged in cutting-edge research into the clinical applications of iPS (induced pluripotent stem) cell technology. The team is working on the development of regenerative medicine and drug discovery, determined to provide patients with innovative treatment methods.
All vertebrates have what are called "neural crest cells," which play an important role in growth and development. Because neural crest cells have the ability to migrate to different locations of the body and change from one cell type to another (also known as differentiation), their use in cell transplantation therapy holds a lot of promise. I am a member of a team working on the Neural Crest Cell Project 1 at T-CiRA, where we are using this technology to create neural crest cells from iPS cells, a technique that was established by our researcher. Our goal is to use these to produce enteric neurons, nerve cells which make up the nervous system of the gastrointestinal tract, in order to develop new drugs for cell therapy treatment for people with congenital intestinal diseases.
I joined the company in 2008. Having studied cell cloning technology as a student, I was assigned to the reproductive and developmental toxicology group of Takeda safety research division. Reproductive and developmental toxicology is an area of research that focuses on the toxic effects of different substances and chemicals on the reproductive ability of an organism and the development of its offspring. While conducting drug safety assessments, I believed that it might be easier to observe reproductive and developmental toxicity in vitro, that is, in a laboratory setting rather than within living organisms. From this, I decided to focus my research on predicting the adverse effects of compounds on the differentiation process of human iPS cells into neural crest cells; in other words, look at what ways certain substances can stop iPS cells changing into neural crest cells properly. I applied for the Takeda Exploratory Challenge (TEC), in which researchers proposed their own themes and, if successful, could receive funding for their projects. My application was approved, and I was able to fully immerse myself in the research. For a young researcher like me, being provided with both the opportunity and the budget to turn my ideas into reality has been a great motivation, giving me the energy to delve deeper into a topic that interests me, and leading to the progress of today.
With cutting-edge research, experiments often fail, but Takeda’s corporate philosophy known as “Takeda-ism” has “perseverance” at the core. If you're confident that it will work, you don't give up, but instead just continue with the process of trial and error. Also, when it comes to innovation, a sense of fun is essential. When you think outside the box and try unusual combinations that no one has attempted, you may be surprised at what you find—sometimes it works out better than you expect revealing new possibilities.
1 Basic platform and application research toward drug discovery and regenerative medicine using human iPS-derived neural crest cells.
"You get good at what you like doing."
I feel most energized when I'm doing what I'm most passionate about. Even if I get off the orthodox track, I feel positive that as long as I keep doing what I love, I can create something original.
Having applied for the research center in-house project TEC, for which researchers propose their own themes and can obtain a budget to carry out the research, Teruyoshi succeeded in inducing differentiation of neural crest cells, based on research findings by CiRA's Dr. Makoto Ikeya. Currently, as part of the Neural Crest Cell project in T-CiRA, he is working on the development of iPS-cell derived neural crest cells in order to develop a new form of cell therapy treatment.
I am the Takeda research leader for an immunotherapy project that creates immune cells from iPS cells and uses them in therapeutic treatment methods. In my role, I hold discussions with other members, check on the state of progress and data of our research, and decide what action to take next. In immunotherapy, there is a process attracting a lot of attention in recent years known as CAR T-cell therapy, in which T cells are extracted from the patient's own blood, modified using gene therapy technology, and then returned to the patient by infusion. However, although generally being a highly successful treatment, one major hurdle is that it is personalized, which means it takes time and a lot of money to prepare the custom-made cells. So, what we are aiming to achieve is what is known as allogeneic transplantation, where stem cells are taken from a matching donor and then infused into the patient's bloodstream. If we are able to transplant mass-produced iPSC-derived immune cells, it will reduce the economic burden on patients and shorten the waiting time for transplantation, making it a treatment option for patients in the future.
Since becoming a project member, I have been struck by the speed and volume of research that T-CiRA enables. In fact, the iPS cell-derived CAR T-cell therapy that we are currently focusing on is expected to provide a breakthrough treatment for blood cancer patients. In May 2020, we finalized a contract with Kyoto University’s CiRA Foundation to start production of iPS cell-derived CART-cells for clinical trials. In order to make regenerative medicines available to the medical community as soon as possible, we are now working on the development of immunotherapy using iPS cells, an area in which we are striving to be a front-runner.
The single defining characteristic of T-CiRA as a workplace would probably be expressed best with the word "diversity." We are conducting joint research with professors from Kyoto University in a format we call in Japanese "eating from the same pot of rice." And new science requires a wide range of expertise, so Takeda's research team is itself made up of members with many different career backgrounds. We also work closely with the Boston research team in order to expand our global reach. While learning about leadership and how to work in such a diverse environment, I think that I have grown a lot, not only as a researcher but also as a person.
"When you feel lost, just move forward."
It is my favorite quote from Senichi Hoshino, a former professional baseball manager. There are many times when I experience doubt, in carrying out research or as a team leader, but I never look back, and the idea of moving forward always guides my decisions.
Yoshiaki is a Takeda research team leader working together with Dr. Shin Kaneko of CiRA to develop new immunotherapy using iPS cell-derived T cells. Currently, he is focusing on iPS cell-derived CAR T-cell therapy for blood cancer patients, with the aim of holding clinical trials in the near future.
I am working to create iPS-cell-derived beta cells, the cells found in the pancreas that secrete insulin, with the aim of developing a new practical treatment for type I diabetes. The key to this research is replicating the environment created over several months in the human womb in a test tube. However, the combinations of conditions and factors are limitless, so if the condition of the original cells varies even slightly, the quality of the cells we produce will be different even if the same process is carried out. For this reason, we repeatedly run a trial-and-error process in order to find a stable method to produce cells of a consistent quality among the tens of thousands of conditions. It takes a month to test just one condition, and any promising methods that show potential require a 6-month efficacy evaluation test. So, the satisfaction of seeing positive results is all the greater.
As a researcher, I'm always conscious that when in doubt, I just need to go back to the starting point—asking what is best for the patient. This question lies at the heart of our corporate philosophy known as “Takeda-ism,” and by reflecting on this the way ahead becomes clear. Type 1 diabetes patients who are waiting for islet cell transplants need treatments that are safer, easy to use and more effective—all important aspects of reducing the burden of treatment.
Sometimes it is also important to take a step outside the laboratory and talk with researchers in other departments so as not to develop too narrow a perspective. Having such discussions can often give rise to new ideas or help you see things from a different perspective.
At home, I have two sons, now aged five and eight, and they keep me very busy every day. Thanks to our flexible work-from-home systems, I can use my time efficiently and take on big projects while also spending time with my children.
Being able to organize my life in a way that takes account of both their routines and my own is very motivating, and I’m also grateful for the understanding and support of my colleagues. Ultimately, this means that I can continue to focus on research that will lead to delivering safer products more quickly to patients.
"Where there’s a will, there's a way."
In pursuing my research or balancing my work and childcare, I sometimes face some obstacles, but whenever I hit a wall, these inspiring words always help me to keep challenging myself without fear of failure.
Since joining the company, Noriko has participated in research into creating pancreatic beta cells from iPS cells. In Pancreatic Beta Cell Therapy Project 2 she has continued her work as a core researcher of pancreatic beta cells and has succeeded in producing iPS cell-derived islet-like cells (iPSC). The aim is to enable the clinical application of these in combination with medical devices.
2 Research on cell therapy for type 1 diabetes.